CDKN2A promoter methylation

Our findings demonstrate that CDKN2A downregulation in glioblastoma cells is associated with decreased cell viability, enhanced drug resistance, increased self-renewal capacity, and altered expression of pluripotency markers. The observed CDKN2A expression changes are mediated by promoter methylation. These results highlight the potential role of CDKN2A as a therapeutic target and prognostic marker in glioblastoma.

Importantly, PI3K inhibitor sensitivity was not necessarily a cancer cell-intrinsic property, and the tumor microenvironment impacts therapeutic response and supports CSCs. Additionally, combined inhibition of EGFR with PI3K inhibitor diminished EGFR activation induced by PI3K inhibitor and potently inhibited cancer cell proliferation and CSC maintenance.

Our study further enlightens the molecular background of BE and EAC. To the best of our knowledge, this is one of the largest studies addressing a targeted analysis of genetic and epigenetic modifications simultaneously across a combined series of non-dysplastic BE and EAC samples.

In summary, mucosal, conjunctival, and cutaneous melanomas show a surprisingly similar global DNA methylation profile and identification of the site of origin by DNA methylation testing is likely not feasible. Still, our study demonstrates tumor location-dependent differences of promoter methylation frequencies in specific cancer related genes together with tumor site-specific enrichment for specific chromosomal changes and genetic mutations.

These data agree with our re-analysis of 2,328 previously published cases (LTS n=465) (Richardson et al., 2020). While there is no definitive molecular signature that guarantees long-term survival in glioblastoma patients in this dataset, these results suggest a constellation of clinical and molecular features that may help guide clinical decision making and predict which patients have the best odds of long-term survival.

There was significant association between methylated states of CDKN2A and high concentrations of 1-OHP in urine (p < 0.01). We identified significant association between polymorphism of GSTs genes and epigenetic silencing of tumor suppressor gene CDKN2A in esophageal squamous cell carcinoma.

In conclusion our results suggest that the sputum is a useful noninvasive tool to identify the epigenetic alteration such as gene promoter methylation. Further, as per the findings of the present study we concluded that the potential of MSP based molecular characterization may be a useful molecular technique for early detection of lung cancer.